Morphine potentiation of ethanol-induced gastric mucosal damage in the rat. Role of local sensory afferent neurons.
Local capsaicin-sensitive sensory afferent neurons may regulate the ability of the gastric mucosa to withstand challenge. Since opioids can modulate the activity of afferent neurones by actions at peripheral sites, the effects of morphine on gastric mucosal damage has been investigated in the rat. Morphine (3-9 mg.kg-1 i.v.) dose-dependently augmented the damage induced by a 5-min intragastric challenge with ethanol (25%-100%), as assessed by macroscopic and histological evaluation. These effects of morphine were significantly inhibited by the opioid antagonists naloxone and the peripherally acting N-methylnalorphine. Pretreatment of rats with capsaicin 2 weeks before the study to induce functional ablation of primary afferent neurons likewise significantly augmented the damage induced by ethanol. Both morphine administration and capsaicin pretreatment substantially augmented histologically assessed damage to the glandular mucosa and enhanced deep hemorrhagic damage following challenge with the low ethanol concentrations, with the appearance of macroscopically distinct antral damage. The enhanced damage induced by 50% ethanol in capsaicin-pretreated rats was not further enhanced by morphine administration, suggesting actions on a common mechanism. These findings support a pathophysiological role for activation of local opioid-sensitive afferent neurons in the modulation of mucosal injury following challenge.
Esplugues
J V
JV
Department of Pharmacology, Wellcome Research Laboratories, Beckenham, Kent, United Kingdom.
Whittle
B J
BJ
D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000633:toxicity*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000294:innervation; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009475:Neurons, Afferent / Q000502:physiology*; D011292:Premedication; D051381:Rats; D011919:Rats, Inbred Strains
D000431:Ethanol; D009020:Morphine; D002211:Capsaicin